Each year, Nature Biotechnology highlights companies that have received sizeable early-stage funding in the previous year. Gate Bioscience wants to tailor gates that stop problematic proteins at the source.

Bacteria evolve mechanisms to compete for limited resources and survive in new niches. Here we study the mechanism of isethionate import from the sulfate-reducing bacterium Oleidesulfovibrio alaskensis. The catabolism of isethionate by Desulfovibrio species has been implicated in human disease, due to hydrogen sulfide production, and has potential for industrial applications. O. alaskensis employs

The fusion of egg and sperm requires an egg surface protein, JUNO in mammals or Bouncer in fish, and several conserved sperm surface proteins, including IZUMO1, SPACA6, DCST1 and DCST2. The binding of JUNO and IZUMO1 is known but is not sufficient for fusion, and the specific roles of SPACA6 and DCST1/DCST2 remain unclear. Deneke, Blaha et al. have now identified a conserved sperm complex that includes

The aberrant aggregation of the presynaptic protein α-synuclein (α-syn) is a hallmark of synucleinopathies, which include Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Previous studies have suggested that α-syn can undergo liquid–liquid phase separation (LLPS) and transition from a liquid to a solid state, which contributes to aggregation and fibril formation. However

Forkhead box protein A1 (FOXA1) is a pioneer transcription factor that binds to chromatin at a canonical DNA motif. This binding promotes the opening of chromatin, providing access to additional transcription factors. Targeting transcription factors such as FOXA1 with small molecules can serve as a useful tool to elucidate the rapid dynamics of transcriptional regulation, but remains difficult owing

Plant and animal stem cells receive signals from their surrounding cells to stay undifferentiated. In the Arabidopsis root, the quiescent center (QC) acts as a stem cell organizer, signaling to the neighboring stem cells. WOX5 is a central transcription factor regulating QC function. However, due to the scarcity of QC cells, WOX5 functions in the QC are largely unexplored at a genomic scale. Here,

Protein complexes composed of strictly essential subunits are abundant in nature and often arise through the gradual complexification of ancestral precursor proteins. Essentiality can arise through the accumulation of changes that are tolerated in the complex state but would be deleterious for the standalone complex components. While this theoretical framework to explain how essentiality arises has

The active site Cys residue in glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is sensitive to oxidation by hydrogen peroxide (H2O2), with this resulting in enzyme inactivation. This re-routes the carbon flux from glycolysis to the pentose phosphate pathway favoring the formation of NADPH and synthetic intermediates required for antioxidant defense and repair systems. Consequently, GAPDH inactivation

Protein kinase A (PKA) is a basophilic kinase implicated in the modulation of many cell-signaling and physiological processes. PKA also contributes to cancer-relevant events such as growth factor action, cell cycle control, cell migration and tumor metabolism. Germline and somatic mutations in PKA, gene amplifications, and chromosome rearrangements that encode kinase fusions, are linked to a growing

Erythrokeratodermia variabilis et progressiva (EKVP) is a rare hereditary skin disorder characterized by hyperkeratotic plaques and erythematous patches that progressively worsen with age. This disorder has been associated with variants in three connexin encoding genes (GJA1, GJB3, GJB4) and four unrelated genes (KRT83, KDSR, TRPM4, PERP). Most cases of connexin-linked EKVP exhibit an autosomal dominant

Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas

Duchenne muscular dystrophy (DMD) gene encodes dystrophin, a large multi-domain protein. Its non-functionality leads to dystrophinopathies like DMD and Becker muscular dystrophy (BMD), for which no cure is yet available. A few therapies targeted towards specific mutations can extend the lifespan of patients, although with limited efficacy and high costs, emphasizing the need for more general treatments

Most processes of life are the result of polyvalent interactions between macromolecules, often of heterogeneous types and sizes. Frequently, the times associated with these interactions are prohibitively long for interrogation using atomistic simulations. Here, we study the recognition of N6-methylated adenine (m6A) in RNA by the reader domain YTHDC1, a prototypical, cognate pair that challenges simulations

TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein predominantly localized in the nucleus under physiological conditions. TDP-43 proteinopathy, characterized by cytoplasmic aggregation and nuclear loss, is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Thus it is crucial to understand the molecular

The human gastrointestinal tract is a competitive environment inhabited by dense polymicrobial communities. Bacteroides, a genus of Gram-negative anaerobes, are prominent members of this ecological niche. Bacteroides spp. uses a repertoire of mechanisms to compete for resources within this environment such as the delivery of proteinaceous toxins into neighbouring competitor bacteria and the ability

Dysregulated branched chain amino acid (BCAA) metabolism has emerged as a key metabolic feature associated with the obese insulin resistant state, and adipose BCAA catabolism is decreased in this context. BCAA catabolism is upregulated early in adipogenesis, but the impact of suppressing this pathway on the broader metabolic functions of the resultant adipocyte remains unclear. Here, we use CRISPR/Cas9

The cell cycle regulator Aurora-A kinase presents an attractive target for cancer therapies, though its inhibition is also associated with toxic side effects. To gain a more nuanced understanding of Aurora-A function, we applied shotgun proteomics to identify 407 specific protein partners, including several splicing factors. Supporting a role in alternative splicing, we found that Aurora-A localizes

Sigma-1 receptor (S1R) is a multimodal chaperone protein which is implicated in various pathophysiological conditions including drug addiction, Alzheimer's disease and amyotrophic lateral sclerosis (ALS). S1R interacts with various ion channels and receptors on endoplasmic reticulum or plasma membrane (PM). It has been reported that S1R colocalizes with the M2-muscarinic acetylcholine receptor (M2R)

The complex mechanism of synaptic vesicle fusion with the plasma membrane for neurotransmitter release is initiated by the formation of the SNARE complex at the presynaptic terminal of the neuron. The SNARE complex is composed of four helices contributed by three proteins: one from syntaxin (localized at the plasma membrane), one from synaptobrevin (localized at the synaptic vesicle), and two from

CD320 is a cell surface receptor that mediates vitamin B12 uptake in most tissues. To date, the mechanisms that regulate CD320 expression on the cell surface are not fully understood. In this work, we studied CD320 expression in transfected human embryonic kidney (HEK) 293 and hepatoma HepG2 cells. By glycosidase and trypsin digestion, monensin and brefeldin treatment, western blotting, flow cytometry

The Nem1-Spo7 phosphatase complex plays a key role in lipid metabolism as an activator of Pah1 phosphatidate phosphatase, which produces diacylglycerol for the synthesis of triacylglycerol and membrane phospholipids. For dephosphorylation of Pah1, the Nem1 catalytic subunit requires Spo7 for the recruitment of the protein substrate and interacts with the regulatory subunit through its conserved region

Molecular conjugation to antibodies has emerged as a growing strategy to combine the mechanistic activities of the attached molecule with the specificity of antibodies. A variety of technologies have been applied for molecular conjugation; however, these approaches face several limitations, including disruption of antibody structure, destabilization of the antibody, and/or heterogeneous conjugation

Correction to: Nature Biotechnology https://doi.org/10.1038/s41587-022-01637-z, published online 19 January 2023.

Transcription factors (TFs) orchestrating lineage-development often control genes required for cellular survival. However, it is not well understood how cells survive when such TFs are lost, for example in cancer. PU.1 is an essential TF for myeloid fate, and mice with downregulated PU.1 levels develop acute myeloid leukemia (AML). Combining a multi-omics approach with a functional genetic screen,

The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins, which are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S protein from SARS-CoV-2 variants has revealed this structural adaptation at high resolution. The analysis of S trimers in situ on intact virions has the potential to

Wageningen-based agbiotech KeyGene, in collaboration with Chiquita and Wageningen University, develops a banana plant resistant to both Fusarium tropical race 4 (TR4), a fungus capable of devastating entire plantations, and black sigatoka, a widespread leaf disease. The new variety, named Yelloway One, was produced by combining traditional crossbreeding techniques and modern DNA analysis technology

Neoantigen cancer vaccines hold great promise for cancer treatment but are often limited by the immunosuppressive tumor environment. Now, as described in Nature, Redenti et al. have overcome this issue by harnessing the natural capacity of bacteria to colonize tumors and trigger immune responses. They have developed a microbial system that produces and delivers distinct sets of neoantigens to elicit

The first clinical results for an RNA-editing oligonucleotide designed to correct a disease-causing single-base mutation in mRNA have been released. The company, Wave Life Sciences, says the agent WVE-006 restored more than 60% of wild-type functional protein in two individuals with the genetic disorder alpha-1 antitrypsin (ATT; encoded by SERPINA1) deficiency. ATT deficiency affects the liver owing

The US Department of Energy (DOE) in October conditionally committed nearly $3 billion to two companies to scale up the production of sustainable jet fuel made from crops, vegetable oils and animal fats. Gevo in Englewood, Colorado, could receive a loan guarantee of nearly $1.5 billion to build a new jet fuel refinery in Lake Preston, South Dakota. And Montana Renewables could receive about the same

Over 10% of patients with a fatal neurodegenerative disease who received bluebird bio’s FDA-approved gene therapy Skysona (elivaldogene autotemcel) have developed hematological cancers, further highlighting the well-known risks of using lentiviral vectors. The patients were treated with Skysona to slow the progression of cerebral adrenoleukodystrophy (CALD), an X-linked rare inherited neurodegenerative

In this episode, Associate Editor Cláudia Vilhena sits down with Ali Shaib, the lead author of an exciting new study showcasing expansion microscopy and the visualization of individual protein shapes using standard laboratory microscopes. Tune in as Ali and Cláudia explore the “accidental” origins of the study, the importance of mentorship and collaboration, and the democratization of super-resolution

Beer lovers can now enjoy their wildest drink yet thanks to a yeast carried by wasps. AB Biotek from Peterborough in the UK has launched Pinnacle Crisp Sour — a brewer’s ingredient made from Lachancea thermotolerans, a yeast found in the bellies of wasps. Traditional beer uses just four ingredients: grain, hops, yeast and water. Hops add the distinctive bitter flavor, and yeast converts sugar from

Recent patents relating to retroviruses, transposons and other virus-like elements for use in gene transfer and gene therapy.

RNA viruses are omnipresent and can infect a wide range of hosts. Recent efforts to sequence ecological samples have identified tens of thousands of new species, yet uncovering the complete spectrum of RNA virus diversity remains challenging. In a new paper published in Cell, Hou et al. describe a deep learning algorithm, called LucaProt, to advance RNA virus discovery at global scale. LucaProt is

Using insulin to control diabetes can lead to dangerously low blood glucose levels (hypoglycemia). For many years, researchers have worked to engineer an insulin that avoids this risk by adjusting its activity in response to glucose, but so far without success. Writing in Nature, Hoeg-Jensen et al. describe an insulin with a glucose-sensitive switch that reversibly responds to ambient glucose levels

Recent moves of note in and around the biotech and pharma industries.

Iron is an essential element for plants. Iron uptake by plants is highly regulated, but the underlying mechanism is poorly understood. Using a truncated fragment of the iron deficiency-responsive bHLH100 gene promoter, we screened the Arabidopsis transcription factor yeast one-hybrid (Y1H) library and identified the DOF family protein, OBP3, as a crucial component of the iron deficiency-signaling pathway

Glycation-induced stress (G-iS) is a physiological phenomenon that leads to the formation of advanced glycation end-products (AGEs), triggering detrimental effects such as oxidative stress, inflammation, and damage to intracellular structures, tissues, and organs. This process is particularly relevant because it has been associated with various human pathologies, including cancer, neurodegenerative

Cancer stem cells (CSCs) may be dedifferentiated somatic cells following oncogenic processes, representing a subpopulation of cells able to promote tumor growth with their capacities for proliferation and self-renewal, inducing lineage heterogeneity, which may be a main cause of resistance to therapies. It has been shown that the "less differentiated process" may have an impact on tumor plasticity

Unscheduled R-loops usually cause DNA damage and replication stress, and are therefore a major threat to genome stability. Several RNA processing factors, including the conserved THO complex and its associated RNA and DNA-RNA helicase UAP56, prevent R-loop accumulation in cells. Here we investigate the function of ALYREF, an RNA export adapter associated with UAP56 and the THO complex, in R-loop regulation

The development of enzymes with high-temperature resistance up to 100 °C is of significant and practical value in advancing the sustainability of industrial production. Phytase, a crucial enzyme in feed industrial applications, encounters challenges due to its limited heat resistance. Herein, we employed rational design strategies involving the introduction of disulfide bonds, free energy calculation

The introduction of potassium-competitive acid blockers (P-CABs) has been a major innovation in gastric H,K-ATPase inhibition and many laboratories are actively engaged in the development of novel molecules within this class. This work investigates the interaction between H,K-ATPase and tegoprazan, a representative of the P-CABs group, in terms of K+ and H+ binding, through functional and structural

Understanding how natural and engineered peptides enter cells would facilitate the elucidation of biochemical mechanisms underlying cell biology and is pivotal for developing effective intracellular targeting strategies. In this study, we demonstrate that our peptide stapling technique, fluorine-thiol displacement reaction (FTDR), can produce flexibly constrained peptides with significantly improved

Protein lipoylation, a vital lysine posttranslational modification (PTM), plays a crucial role in the function of key mitochondrial TCA cycle enzymatic complexes. In eukaryotes, lipoyl PTM synthesis occurs exclusively through de novo pathways, relying on lipoyl synthesis/transfer enzymes, dependent upon mitochondrial fatty acid and Fe-S cluster biosynthesis. Dysregulation in any of these pathways leads

Amyloid deposits are present in the brains of cognitively impaired individuals, but also accumulate throughout the body. Some biotechs aim to keep these misfolded proteins in check to treat a range of diseases, including heart failure, ALS and Alzheimer’s disease.

Lysosomal damage induces stress granule (SG) formation. However, the importance of SGs in determining cell fate and the precise mechanisms that mediate SG formation in response to lysosomal damage remain unclear. Here, we describe a novel calcium-dependent pathway controlling SG formation, which promotes cell survival during lysosomal damage. Mechanistically, the calcium-activated protein ALIX transduces